American Indian and Alaskan Native lesbian, gay, bisexual, transgendered, and two-spirited individuals (two spirits) are a drastically understudied and underserved group, at risk for multiple health and mental health problems. There are no national, quantitative, representative studies of this population on any topic. This application, in response to PA-01-096, is for a FIRST TIME R01 by a NEW INVESTIGATOR. Building upon solid preliminary data, it proposes three innovative and significant aims. First, we will conduct structured survey interviews with 400 two spirits drawn from six sites across the U.S. With these interview data, we will test a theoretical model of stress and coping specific to this population. Sub-aims are to (a) establish preliminary prevalence rates of trauma and health outcomes (i.e., HIV sexual risk behaviors, alcohol and other drug use, and mental health indicators); (b) test the direct associations between trauma and health outcomes; (c) determine how cultural and spiritual coping factors moderate the effect of trauma on health outcomes; and (d) examine the mediating role of substance use on the trauma-HIV sexual risk behavior and trauma-mental health relationships. The second aim is to test the, feasibility of an innovative non-probability sampling methodology that combines targeted, partial network, and respondent-driven sampling procedures in order to approximate a representative national sample of two spirits. Additionally, we will test the feasibility of two different mechanisms (agency based vs. census based) by which we execute this sampling method. Our results will contribute toward the refinement of a sample strategy useful in studying other hidden and stigmatized populations. Our third and final aim is to conduct a qualitative study involving 12 focus groups and 60 key informant interviews in order to identify emergent themes regarding stressors and coping strategies specific to two spirits. Through the course of this project, we aim to develop the research infrastructure at the six community agencies comprising our participant recruitment sites in order to facilitate future goals of designing and evaluating interventions to address the urgent needs of two spirits.